Tritium-labeled Cholesterol has been used to study several aspects of exogenous cholesterol metabolism in man. The rate and magnitude of the appearance of ingested cholesterol in the various blood compartments has been followed. Fecal excretion of the labeling material was measured. Cholesterol of dietary origin was demonstrated in a human atherosclerotic aorta.

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Previous studies from this laboratory (1, 2) have indicated that when the cholate content of the rat's plasma is elevated, either by biliary obstruction or by the continuous intravenous injection of cholate into normal rats, a hypercholesteremia promptly appears. Moreover, excess cholate was found in the plasma of patients suffering from various states involving hypercholesteremia (3). These findings suggest that this "natural detergent" of the body may be concerned not only in the hypercholesteremia occurring in biliary obstruction but also in that of other conditions.The mechanism by which cholate induces hypercholesteremia was not discovered in these studies, however, although it was found that the cholateinduced hypercholesteremia of the rat did not depend upon an increase in the intestinal absorption of cholesterol (2). More recently it also was found (4) that the mechanism did not involve the possible conversion of cholic acid into cholesterol; nor does it depend upon hemolysis.The present report describes our more recent studies concerning the possible mechanism involved in cholate-induced hypercholesteremia. The evidence obtained indicates that cholate acts in the blood stream. Here it retards the exit of cholesterol from the plasma, leading to a surfeit of cholesterol in the plasma alone. A Comparison of lhe Hypercholesleremia Produced by Biliary Obstruction with That Produced by Continuous Intravenous Injection of Cholate8 Long-Evans strain, male tats, approximately 12 weeks old and weighing between 202 and 308 gin. were fasted for 20 hours but given water and then subjected to biliary obstruction as described in a previous report (5). 19 fasted rats treated in the same way were unilaterally nephrectomized and then given a continuous intravenous injection of 25 rag. of cholic acid per hour as sodium cholate in Tyrode solutions for 24 hours after an initial injection of 25 nag.,

Tritium has been used to study certain aspects of endogenous and exogenous cholesterol metabolism in normal and hypercholesterolemic rabbits. Special attention is given to turnover studies on aortic cholesterol. Labeled cholesterol has been used for feeding experiments an(l the subsequent rise of serum cholesterol specific activity has been investigated.G OFMAN and co-workers' have made observations on the mode of transport of cholesterol in lipoprotein molecules in serum, and have presented evidence to link the appearance of certain of these lipoprotein molecules in human serum with the development of atherosclerosis. A general study of these molecules has been undertaken in this laboratory, directed toward gaining a fuller knowledge of their origin, function and fate, and thus clarifying their position in the pathogenesis of atherosclerosis. Cholesterol metabolism necessarily occupies a position of prominence in this study. Lipoprotein molecules similar to those occurring in human serum are to be found in great concentration in the hypercholesterolemic rabbit laying down atheromas, and for this reason the rabbit has been selected for this preliminary study. This report will present some observations on the fate of exogenous and endogenous cholesterol in normal and hypercholesterolemic rabbits.Rittenberg and Schoenheimer2 showed that in vivo cholesterol synthesis incorporates hydrogen from the body water into the cholesterol molecule, and Bloch and Rittenberg3 prepared deuterium-labeled cholesterol. Thus an opportunity to study certain aspects of endogenous and exogenous cholesterol metabolism is afforded. Tritium has been used in this work for the hydrogen label; tritium-labeled cholesterol was prepared4 using the method of From the Donner